RS54297B1 - TWO-CHAMBER CYLINDER Syringe AND Syringe Filled with ARIPIPRAZOLE - Google Patents

Abstract

A two-chamber pre-filled syringe (100) comprising: a cylinder (10) having a cylindrical shape with a symmetry axis (O) as center and having a bypass portion (11) formed by the projection of one part of the inner circular surface outwards; luer-lock extension (20) located at the front end of the cylinder; handle (60) located at the rear end of the cylinder; front stopper (30) mounted at the front end of the by-pass of the cylinder part; middle stopper (40) is fitted at the rear end of the cylinder by-pass to seal the preparation (S) together behind the front plug; the rear plug (50) fitted to the rear of the middle plug in the cylinder to seal the solvent together with the middle plug; (70) which is attached to the rear plug by a insertion of the handle; an internal threaded portion (64) made to rotate about the axis of symmetry on the inner circumferential surface of the handle; an outer thread ide (73) designed to be screwed with an inner thread on the outer circular surface of the piston, comprising a groove guide (65) formed on the inner thread portion extending parallel to the axis of symmetry; a guide plate (75) formed at the rear of the outer threaded portion of the outer circumferential surface of the plunger and guided in accordance with the groove guide; a first protuberance (66) formed at the rear end of the handle and with which the guide plate is arranged to come into contact with it and to pass over it when at least one portion of the middle stud, which is rotated by the piston according to the rotation of the inner thread and the outer thread portion , moves forward along the by-pass part. The application contains 4 more patent claims.

Description

[0001] This invention relates to a two-chamber pre-filled syringe.

[0002] Pre-filled syringes can be filled with a liquid preparation and thus can be used without problems immediately after they are taken out of the packaging in health institutions. As described above, pre-filled syringes are excellent in terms of practicality and contribute significantly to reducing the workload of medical service providers such as doctors and nurses and are therefore used in many hospitals.

[0003] As a type of pre-filled syringe, two-chamber syringes in which the preparation and solvent or solution (dispersing agent) are separately filled have been known until now.

[0004] The two-chamber pre-filled syringe has a front plug inserted into the front end of the cylinder and an end plug inserted into the rear end of the cylinder and a middle plug inserted into the central part inside the cylinder so that the cylinder is divided into two chambers, front and back. In addition, the bypass part (by-pass) which is formed so that the inner peripheral surface of the cylinder is partially bulged outwards. and it is formed on the part that is closer to the front end than the middle plug of the cylinder. In addition, the powder is sealed in the front chamber at the front of the middle plug, and at the front end it is sealed with a front plug. The solvent is sealed in the back chamber on the back side of the middle plug and at the rear end is sealed with the end plug. The piston is connected to the back of the end plug.

[0005] When using a two-chamber prefilled syringe having this configuration, the end cap is moved forward by pushing the piston into the cylinder. Therefore, the pressure force created by the movement of the end plug over the solvent is transferred to the middle plug, and thus the movement of the end plug also moves the middle plug forward. When the middle plug reaches the bypass, the anterior chamber and the posterior chamber communicate with each other via a bulging bypass. Therefore, the solvent in the back chamber flows into the front chamber and mixes with the preparation in the front chamber, thus reconstituting the injection.

[0006] Aripiprazole used as an active component of a pharmaceutical formulation is known as an atypical antipsychotic used to treat schizophrenia and is expressed by the following structural formula (for example, search in US Patent No. 5006528):

[0007] When, for example, a syringe pre-filled with aripiprazole is used, that is, aripiprazole filled in a syringe is used, the composition is reconstituted in the form of a cake obtained by suspending the pharmaceutical formulation with a dispersing agent and then drying the suspension by freezing. When a cake-form composition is used, it is mixed with a desired dispersing agent (injectable liquid) to resuspend it, and the resuspension is injected into a patient intramuscularly or subcutaneously (for example, according to Japanese Patent Application Publication No. 2007-509148).

[0008] In addition, Japanese patent application, publication no. 8-112333 discloses a pre-filled dual-chamber syringe called a "dual-chamber syringe" in which the lyophilized material is reconstituted by lyophilizing the solution in the syringe and then (hermetically) sealed with a rubber stopper and in which the injectable liquid is (hermetically) sealed in the second septum chamber of the syringe.

[0009] In the above-described pre-filled syringe with a dual chamber, in order to mix the solvent and the preparation, it is necessary that the middle plug be positioned in the bypass until all the solvent that is in the back chamber flows into the front chamber. In addition, it is necessary to control the flow of the solvent in the case of a preparation that does not dissolve easily.

[0010] However, if the piston is pushed prematurely or pushed too hard without confirming that the solvent has flowed into the front chamber, the front plug is moved to be closer to the front end than the bypass is in a state where the entire amount of solvent cannot completely flow out into the front chamber. Because of this, the solvent remains behind in the back chamber without mixing with the preparation.

[0011] In this way, due to the improper operation of the piston, an unusable amount of solvent is created that will not be mixed with the preparation, and as a result, the problem arises that it cannot be reconstitutes an injection of a predetermined concentration and that the preparation is not sufficiently dissolved in the solvent.

[0012] In the case of the above-described aripiprazole, which is filled into a syringe, the problem is caused by the residue resulting from incomplete suspension during resuspension.

[0013] It is desirable to avoid the above-mentioned problems, for example, by providing a pre-filled syringe with a dual chamber in which the solvent and the preparation can be safely and appropriately mixed with each other according to their properties.

[0014] It is desirable to overcome the above-mentioned problems for example by providing aripiprazole filled in a syringe adapted to reduce the residue caused by incomplete suspension during resuspension.

[0015] Japanese Patent Publication No. JP 2514472 B2 describes a two-chamber syringe and a method of application, but does not disclose the combination of features specified in the characterizing part of patent claim 1 listed below.

[0016] The invention provides a two-chamber pre-filled syringe consisting of: a cylinder having a cylindrical shape with an axis of symmetry as the center and having a bypass part formed due to the protrusion of a part of the inner circular surface to the outside, a luer-lock extension located at the front end of the cylinder, a handle located at the rear end of the cylinder, a front plug located at the front end of the peripheral part of the cylinder, a middle plug that is arranged at the rear end of the peripheral part of the cylinder to together behind the front plug hermetically sealed the preparation, the rear plug which is fitted on the back of the middle plug in the cylinder to hermetically seal the solvent together with the middle plug, the piston which is connected with the rear plug from the rear side by inserting the handle, the internally threaded part which is made to rotate about the axis of symmetry on the inner peripheral surface of the handle and the externally threaded part which is made to be able to be screwed with the internal thread on outer circular surface of the piston, indicated by a guide groove formed on the internally threaded part and extending parallel to the axis of symmetry, a guide plate formed on the rear side of the externally threaded part on the outer peripheral surface of the piston and guided in accordance with the guide groove, and a first protrusion formed at the rear end of the handle and with which the guide plate is positioned so as to come into contact with it and pass over it when at least one part of the middle plug, which is moved forward along the circumferential part by turning the piston by screwing the parts with internal and external thread.

[0017] In order for this invention to be better understood, its embodiments will now be described, by way of example only, in relation to the drawings in which: FIG. 1 represents a longitudinal section of a pre-filled two-chamber syringe (aripiprazole filled into a syringe) in accordance with an embodiment,

[0018] FIGURE 2A is a perspective view illustrating a handle,

[0019] FIGURE 2B is a longitudinal section illustrating a handle,

[0020] FIG. 3 represents a side view of the piston,

[0021] FIGURE 4 represents a side view of the piston,

[0022] FIG. 5 represents the appearance of the clip in perspective,

[0023] FIGURE 6A is a view illustrating a method of using a dual-chamber pre-filled syringe according to this embodiment,

[0024] FIGURE 6B is a view illustrating a method of using a dual-chamber pre-filled syringe according to this embodiment,

[0025] FIGURE 6C is a view illustrating a method of using a dual-chamber pre-filled syringe according to this embodiment,

[0026] FIGURE 7A is a view illustrating a method of using a dual-chamber pre-filled syringe according to this embodiment,

[0027] FIGURE 7B is a view illustrating a method of using a dual-chamber pre-filled syringe according to this embodiment,

[0028] FIG. 8 is a perspective view of the handle and the piston inserted inside the handle,

[0029] FIG. 9A represents the appearance of the handle of the modified version, i

[0030] FIG. 9B represents the appearance of the handle of the modified version.

[0031] When using a two-chamber pre-filled syringe having the features of one of the embodiments of the present invention, the plunger can rotate in accordance with the screwing of the externally threaded portion and the internally threaded portion. Therefore, the piston is gradually moved forward in accordance with the steps of the part with the external thread and the part with the internal thread. Therefore, it is possible to avoid an excessive speed of the forward movement of the piston and thus allow the middle plug to remain in the bypass. Accordingly, the flow rate of the solvent into the front chamber can be easily adjusted and kept constant, and it is possible to effectively mix the preparation in the solvent.

[0032] In addition, in the two-chamber pre-filled syringe according to the embodiment of the present invention, when the intermediate plug which is moved forward by pushing the piston enters the bypass part, the front end of the externally threaded part presumably reaches the rear end of the internally threaded part and can be screwed into it.

[0033] When the middle plug is moved forward over the rear plug and the solvent by pushing the piston, the front end of the externally threaded portion contacts the rear end of the internally threaded portion as the middle plug enters the bypass portion. Therefore, even when the piston is still pressed, it no longer moves forward and the middle plug also does not move. Therefore, it is possible to avoid that due to excessive force acting on the piston, the middle plug moves too much towards the front end of the bypass part.

[0034] Moreover, after the front end of the external thread is brought into contact with the rear end of the internal thread as described above, the piston is gradually moved forward according to the screwing of the externally threaded portion and the internally threaded portion by turning the piston. When the middle plug is moved forward by moving the piston and completely enters the bypass part, the solvent is introduced into the preparation through the bypass part and both are mixed. The flow of the solvent into the preparation is adjusted by the pitch of the internal and external threads, and thus the flow rate at which the preparation is easily dissolved can also be adjusted.

[0035] So, after the piston can rotate in accordance with the screwing of the external to the internal thread, only when the middle plug reaches the bypass part and the solvent is introduced into the preparation, the operation of pushing the piston can be performed until the middle plug reaches the bypass part. Therefore, it is possible to avoid unreliable handling of the two-chamber pre-filled syringe.

[0036] The meaning of the phrase "when the middle plug enters the bypass" includes when the front end of the middle plug reaches the rear end of the bypass, when the middle plug part enters the bypass, and just before the front end of the middle plug reaches the rear end of the bypass. Namely, a configuration can be provided in which the front end of the externally threaded portion reaches the rear end of the internally threaded portion just before the front end of the middle plug reaches the bypass portion.

[0037] In addition, the two-chamber prefilled syringe further comprises: a guide groove which is formed in the internally threaded part and extends parallel to the axis of symmetry and a guide plate which is formed at the rear end of the externally threaded part on the outer peripheral surface of the piston and which is directed by the guide groove.

[0038] When the piston is rotated and moved forward by screwing the externally threaded part into the internally threaded part, the externally threaded part of the piston passes through the internal thread of the handle until it passes completely through and the threads are released and the piston can be pushed. At that moment, for example, the piston stops in a position where the piston guide plate and the guide groove formed in the internal thread can fit into each other. Therefore, by pushing the piston, it can be guided in the direction in which the groove extends. Thanks to this, the piston can safely go from rotating to straight, and by allowing the piston to go straight, it is possible to safely squeeze out the bubbles that are in the cylinder and inject the liquid preparation into the patient.

[0039] In addition, the two-chamber pre-filled syringe further includes: a first protrusion formed at the rear end of the handle and with which the guide plate is brought into contact to be able to pass when at least one part of the middle cap, which is moved forward by turning the piston in accordance with the rotation of the inner stem part and the outer stem part, is moved over the bypass part.

[0040] When the middle plug portion moving forward in the cylinder is moved over the bypass portion by turning and moving the piston forward in accordance with the screwing of the internally threaded portion and the externally threaded portion, the piston guide plate is brought into contact with the first protrusion. Therefore, after the middle plug part is moved over the bypass part, the healthcare worker can easily recognize that the space between the middle plug and the front plug, namely the space where the solvent and preparation are mixed, is resealed. Then the healthcare worker shakes the two-chamber syringe and thus can reconstitute the injection in which the preparation is completely mixed, dissolved or suspended in the solvent.

[0041] Furthermore, in a two-chamber pre-filled syringe, after the guide plate passes over the first protrusion by turning the plunger in accordance with the external and internal threads, preferably there is a release from the screw between the externally threaded portion and the internally threaded portion.

[0042] Accordingly, after the middle plug part moves over the bypass part due to the rotation and forward movement of the piston in accordance with the screwing of the external and internal threads, the piston can be pushed. Namely, after the piston turns only when the solvent is introduced into preparation and then the operation is switched to piston pushing operation, the handling of the two-chamber pre-filled syringe can be simplified. Additionally, after the guide plate is brought into contact with the first protrusion before the screw between the external and internal threads is released, the end of rotation of the piston can be detected by the healthcare professional in advance.

[0043] In addition, the two-chamber pre-filled syringe further includes: a second protrusion formed at the rear end of the handle which is contacted at a point where the guide plate passing over the first protrusion can be placed in the guide groove.

[0044] When the guide plate crosses the first protrusion as described above, the external thread of the piston and the internal thread of the handle are released from the screwing, and thus the movement of the piston forward by turning is switched to moving in a straight line. In addition, at the same time, the guide plate is brought into contact with the second protrusion, and thus the health worker recognizes that the piston can be pushed. Namely, the way the piston works can be safely changed by contacting the guide plate with the second protrusion. Furthermore, in this state, the guide plate and the guide groove can be placed inside each other. So, after that, by pushing the piston, it can move forward along the water plate.

[0045] Furthermore, the preparation presumably includes aripiprazole.

[0046] Namely, although aripiprazole is difficult to dissolve in a solvent, the preparation can be properly dissolved in a solvent in a two-chamber pre-filled syringe of the configuration described above. Therefore, even when aripiprazole is used as a preparation, aripiprazole can easily be suspended in a solvent.

[0047] In addition, the aripiprazole-filled syringe according to an embodiment of the invention includes: aripiprazole, a cylinder having a cylindrical shape with an axis of symmetry as the center and a bypass portion created by bulging a portion of the inner circular surface outward, a luer-lock extension provided at the front end of the cylinder, a handle provided at the rear end of the cylinder, a front cap placed on the side of the front end of the bypass portion in the cylinder, a middle cap placed on the rear end side of the bypass parts in the cylinder to hermetically seal the aripiprazole together with the front cap, the end cap which is placed on the back end side of the middle cap in the cylinder to hermetically seal the solvent together with the middle cap, the piston which is connected with the end cap from the rear end by inserting the handle, the internally threaded part on the inner peripheral surface of the handle made to screw about the axis of symmetry, and the externally threaded part on the outer peripheral surface of the piston made to be able to screws into the internally threaded part.

[0048] When using aripiprazole filled in a syringe according to an embodiment of the invention, the piston rotates in accordance with the screwing of the part with the external thread and the part with the internal thread. Accordingly, the piston gradually moves forward in accordance with the pitch of the external and internal threads. Therefore, it is possible to avoid the excessive speed of the forward movement of the piston and thus it is possible to ensure that the middle plug remains in the bypass part. Accordingly, the solvent flow rate into the front chamber can be easily adjusted and made constant and it is possible to reduce the residue during resuspension.

[0049] According to the exemplary embodiment of the two-chamber pre-filled syringe of the present invention, it is possible to avoid excessive forward movement speed of the piston and thus it is possible to prevent the middle plug from moving too far forward and out of the bypass. Thus, it is possible to enable the middle plug to easily remain in the bypass and to adjust the solvent flow rate by means of external and internal thread steps, which makes it possible to properly mix the solvent and the preparation.

[0050] In addition, with regard to aripiprazole filled in a syringe, it is possible to reduce the residue and incomplete dissolution during resuspension.

[0051] In the following text, the two-chamber prefilled syringe and the aripiprazole filled into the syringe in accordance with the embodiments of the present invention will be described in detail with reference to the drawings.

[0052] As shown in FIG. 1, a two-chamber pre-filled syringe (aripiprazole pre-filled syringe) 100 is provided with a cylinder 10, a luer-lock attachment 20, a front cap 30, a middle cap 40, an end cap 50, a handle 60 and a plunger 70. In this two-chamber pre-filled syringe 100, preparation S and solvent L to be mixed together with the other to reconstitute injection M (see FIG. 7A) are filled in a separated state.

[0053] The two-chamber pre-filled syringe 100 of this embodiment is suitable to be used for injectable material such as preparation S which does not dissolve easily in the solvent and even in that case the preparation S can be easily and safely dissolved and suspended in the solvent L. The value of the two-chamber pre-filled syringe 100 of this embodiment is shown especially when aripiprazole is used as preparation S which does not dissolve easily in the solvent

[0054] L.

[0055] Aripiprazole, namely 7-{4-[4-(2,3-dichlorophenyl)-1-piperazine]butoxy}-3,4-dihydrocarbostyril or 7-{4-[4-(2,3-dichlorophenyl)-1-piperazine]butoxy}-3,4-dihydroquinolin-2(1 H)-one is an atypical antipsychotic drug useful for the treatment of schizophrenia and has the following structural formula:

[0056] The cylinder 10 is cast from transparent glass and has an approximately cylindrical shape that extends along the axis of symmetry 0. The approximately central part of the cylinder 10 in the direction of the axis of symmetry O is formed as a bypass part 11 in which part of the outer circular surface and the inner circular surface of the cylinder 10 in the peripheral direction is bulging outward radially by a predetermined dimension in the direction of the axis of symmetry O. The position of the bypass part 11 in the direction of the axis of symmetry 0 can be appropriately placed according to the construction.

[0057] In addition, the cylindrical part of the cylinder 10 on the side of the front end of the bypass part 11 is formed as the front part of the cylinder 12 and the cylindrical part of the bypass part 11 on the side of the rear end is formed as the back part of the cylinder 13. Namely, the cylinder 10 has the front part of the cylinder 12 which is located on the side of the front end of the bypass part 11 as a border and the rear part of the cylinder 13 which is located on the side of the rear end. Namely, in the cylinder 10, the space on the side of the front end is formed as the front part of the cylinder 12, the space on the side of the rear end is formed as the rear part of the cylinder 13 and the space between the space on the front side and the space on the back side is formed as the bypass part 11.

[0058] In addition, an annular front overhang 14, which protrudes radially outward over the entire circular surface, is formed on the outer rim at the front end of the cylinder 10. Furthermore, an annular rear overhang 15, which radially protrudes outward over the entire circular surface, is formed on the outer rim at the rear end of the cylinder 10.

[0059] The luer-lock extension 20 is cast from a transparent synthetic resin of appropriate rigidity and has a multi-stage shape on the outside with the axis of symmetry O as the center. The luer-lock attachment 20 has a base 21 of a cylindrical shape, a cylindrical part 22 which is connected to the front end of the base 21 so as to be reduced in diameter by one degree, and a luer tip 23 which is formed on the side of the front end of the cylindrical part 22 so that it has a smaller diameter than the cylindrical part 22. The adjustment opening 24 which is open to the rear side of the luer-lock attachment 20 is formed inside the base 21 and the bypass chamber 25 having the shape of a hole with a bottom is formed on the front side of the adjustment opening 24, namely inside the cylindrical part 22. The front surface 25a with which the front end of the front plug 30 is brought into contact is formed at the place that contacts the bottom of the bypass chamber 25. The front surface 25a is formed in the form of a conical surface, the diameter of which gradually decreases towards the front side.

[0060] In addition, an inlet opening 23a pierced along the axis of symmetry O is formed inside the luer tip 23. One end of the inlet opening 23a is open to the front end of the luer tip 23 and the other end is open to the center of the front surface 25a of the bypass chamber 25. The injection needle 27 (which is omitted in FIG. 1, see FIG. 7B) which goes to the front end along the axis of symmetry O is attached to one end, ie. the front end of the inlet opening 23a so that it communicates with it. A protective cap 110 is placed on the luer tip 23.

[0061] The fitting opening 24 is made to attach the luer-lock extension 20 to the cylinder 10 and its inner diameter is made to be approximately the same as the outer diameter of the cylinder 10. The luer-lock extension 20 is attached to the front end of the cylinder 10 so that the fitting opening 24 encircles the front end of the cylinder 10.

[0062] In addition, a circularly recessed annular groove 24a is formed at the front end of the inner circular wall of the fitting hole 24 with the symmetry axis O as the center. When the luer-lock fitting 20 is placed on the front end of the cylinder 10, the annular front overhang 14 of the cylinder 10 is fitted into the annular groove 24a and thus the luer-lock fitting 20 is hermetically, liquid-tight and rigidly integrally fixed to the cylinder 10.

[0063] The bypass chamber 25 described above has an opening with a bottom whose inner diameter is one degree smaller than the diameter of the fitting hole 24 and whose inner circular wall has a bypass groove 26 made on it. The bypass groove 26 consists of a straight groove 26a and a circular groove 26b.

[0064] More than one rectilinear groove 26a is formed on the inner surface of the wall of the bypass chamber 25 at regular intervals in a circle so that they run parallel to the axis of symmetry O and the front ends of these rectilinear grooves 26a are connected to the opening opening 23a extending to the front surface 25a from the inner side of the wall of the bypass chamber 25 and formed inside the luer tip 23.

[0065] In addition, the circular groove 26b is a circular groove that goes circularly in the direction of the axis of symmetry O as the center and is formed near the boundary between the adjustment opening 24 and the bypass chamber 25 on the surface of the inner wall of the bypass chamber 25. The circular groove 26b is connected to the corresponding ends of the above-described plurality of rectilinear grooves 26a, and thus the respective rectilinear grooves 26a are connected via circular groove 26b.

[0066] The front plug 30, the middle plug 40 and the end plug 50 are molded from medical rubber which is resistant to corrosion caused by preparation S, solvent L and injection M and have an approximately cylindrical shape whose outer diameter is slightly larger than the inner diameter of the cylinder 10, with the axis of symmetry O as the center.

[0067] The front plug 30 is placed at the front end of the bypass part 11 of the cylinder 10, namely it is placed in the front part of the cylinder 12.

In addition, the middle plug 40 is placed at the rear end of the bypass part 11 of the cylinder 10, namely it is placed in the rear part of the cylinder 13. In particular, the middle plug 40 of this embodiment is arranged so that the middle plug 40 is placed at the border between the bypass part 11 and the rear part of the cylinder 13. The powder preparation S is sealed so that it is sandwiched between the middle plug 40 and the front plug 30 in the cylinder 10. Namely, the preparation S is filled in the front chamber F, which is formed by the inner circular surface of the cylinder 10, the back side of the front plug 30 and the front side of the middle plug 40.

[0069] The end plug 50 is placed from the rear side of the middle plug 40 at the far end of the rear part of the cylinder 13 of the cylinder 10 away from the middle plug 40 in the direction of the axis of symmetry O. The solvent L which is in liquid form is sealed so as to be sandwiched between the end plug 50 and the above-described middle plug 40. Namely, the solvent L is filled in the rear chamber B formed by the inner circular surface of the cylinder 10. the rear surface of the middle plug 40 and the front surface of the end plug 50. An internally threaded opening (omitted), into which the connecting part 76 of the piston 70 to be described later is screwed, is formed at the rear end of the end plug 50.

[0070] In this way, in the two-chamber pre-filled syringe 100, the preparation S and the solvent L are separately hermetically sealed in the front chamber F and the back chamber B separated by the middle plug 40.

[0071] As shown in FIGURES 2A and 2B, the handle 60 is provided with a mounting part 61, a flange part 62 and a cylindrical part 63.

[0072] The mounting part 61 has an approximately cylindrical shape with the axis of symmetry O as the center and the mounting hole 61a, to which the rear end of the cylinder 10 formed on the inner peripheral side of the mounting part 61 is attached. The annular groove 61b which is circularly recessed is formed on the inner periphery of the rear end of the mounting hole 61a with the axis of symmetry O as the center. As shown in FIG. 1, when the handle is attached to the rear end of the cylinder 10, the ring-shaped rear overhang 15 of the cylinder 10 enters the ring groove 61b, and thus the handle 60 is firmly and integrally fixed to the cylinder 10.

[0073] The flange portion 62 protrudes diametrically from the rear end of the mounting portion 61, namely from the boundary between the mounting portion 61 and the cylindrical portion 63 with the axis of symmetry O as the center and has an approximately rectangular shape when viewed in the direction of the axis of symmetry O. The flange portion 62 supports the fingers of the health care worker when the two-chamber pre-filled syringe 100 is used and thus the handling of the two-chamber pre-filled syringe 100 makes it simple for the healthcare professional.

[0074] The cylindrical part 63 has an approximately cylindrical shape with the axis of symmetry O as the center and further extends towards the rear side from the rear end of the mounting part 61. The cylindrical part 63 has an inner diameter which is one degree smaller than the inner diameter of the mounting part 61 and a step at the boundary between the cylindrical part 63 and the mounting part 61 is brought into contact with the rear end of the cylinder 10. The internally threaded part 64 which twists around the axis of symmetry O is formed on the inner circular surface of the cylindrical part 63. The internally threaded part 64 consists of two internal threads that are twisted in a clockwise direction (hereinafter referred to as the direction of rotation of the screw) toward the front side from the back of the handle 60, and each external thread extends to turn, for example, 360° of the inner circular surface of the cylindrical part 63.

[0075] In addition, a guide groove 65 which is recessed outwards (from the outside in the radial direction of the symmetry axis O) in the radial direction of the internally threaded part 64 and runs parallel to the symmetry axis O is made on the inner circular surface of the cylindrical part 63, namely in the internally threaded part 64. This guide groove 65 goes over the entire surface of the cylindrical part 63 and the inner part with thread 64 in the direction of the axis of symmetry O and a pair of guide grooves 65 are provided to stand opposite each other at a distance of 180° in the circular direction of the part with internal thread 64, namely opposite each other in the diametrical direction of the part with internal thread 64.

[0076] In addition, a pair of first protrusions 66 and a pair of second protrusions 67 are provided at the rear end of the cylindrical part 63. The pair of first protrusions 66 is intended to be opposite each other at an interval of 180° in the circular direction of the cylindrical part, namely opposite to each other in the diametrical direction of the cylindrical part. In addition, a pair of other protrusions 67 are provided to be opposite each other at an interval of 180° in the circular direction of the cylindrical part, namely opposite to each other in the diametrical direction of the cylindrical part.

[0077] The first protrusion 66 is formed on the part near the rear side of the pair of guide grooves 65 of the rear surface 63a of the cylindrical part 63 in the direction of rotation by twisting to protrude toward the rear side along the symmetry axis O from the rear surface 63a. In addition, the second protrusion 67 is formed at the portion near the front side of the pair of guide grooves 65 of the rear surface 63a of the cylindrical part 63 in the direction of rotation by screwing to protrude toward the rear side along the symmetry axis O from the rear surface 63a. The first and second protrusions 66 and 67 are adjacent to the guide grooves 65 so that the guide grooves 65 are sandwiched between them circularly in the direction of the axis of symmetry O.

[0078] Here, the surface of the first protrusion 66 facing the rear side in the screw rotation direction is made as a slightly inclined surface 66a which is gradually inclined toward the rear side along the symmetry axis O from the rear surface 63a facing the front side in the screw rotation direction. In addition, the surface facing the front side of the screw rotation direction of the first protrusion 66 is made as a steeply inclined surface 66a which is gradually inclined to the front side along the symmetry axis O facing the front side of the screw rotation direction. The steeply sloping surface 66b has a greater slope than the slightly sloping surface 66a described above.

[0079] In addition, the surface of the second protrusion facing the rear side in the direction of screw rotation is made as a vertical surface 67a that goes vertically to the rear side along the symmetry axis O from the rear surface 63a of the cylindrical part 63 connected to the guide grooves 65.

[0080] The second protrusion 67 is made to be higher than the first protrusion 66, namely, the upper part of the vertical surface 67a of the second protrusion 67 is located closer to the rear side in the direction of the symmetry axis O than the upper part of the first protrusion 66.

[0081] The piston 70 is a member connected to the end plug 50 to move the end plug 50 toward the front side of the cylinder 10. As shown in FIGURES 3 to 5, the piston 70 has a long portion of the piston 71 extending along the axis of symmetry O, a connecting portion 76 located at the front end of the long portion of the piston 71 and having the form of an external thread attached to the end plug 50 and pressing part 77 which is located at the rear end of the long part of the piston 71 and with which the healthcare worker exerts pressure when pushing the end plug 50.

[0082] In addition, an external thread 73 that is twisted around the axis of symmetry 0 is formed on the outer circular surface of the long part of the piston 71. The external thread 73 is composed of two external threads that are twisted in a clockwise direction (the direction of rotation by screwing) from the back to the front end of the piston 70. This external thread 73 is formed along a predetermined span in the direction of the axis O more towards the front end rather than the central part of the long part of the piston 71 in the direction of the axis of symmetry O.

[0083] The long part of the piston 71 has a pair of cutouts 74 which are formed by cutting in a predetermined length circularly along almost the entire surface in the direction of the axis of symmetry O. This pair of cutouts 74 are made with a mutual distance of 180° circularly on the long part of the piston 71. Therefore, the long part of the piston 71 can be cast in a two-part mold.

[0084] The outer thread 73 is divided into two parts by the cuts 74 along the circumference of the long part of the piston 71.

[0085] In the section 74, a rib 74a is formed which protrudes outwards radially from the axis of symmetry O from the lower surface of the section 74, namely from the surface of the section 74 which faces outwards radially from the axis of symmetry O so that it runs parallel to the axis O. The rib 74 gives strength to the long part of the piston 71. In addition, two ribs 74a are placed parallel to the axis of symmetry O in the corresponding sections 74. Thanks to this configuration in which the rib 74a on the front side and the rib 74a on the rear side are thus separated, it can be avoided that a part of the solvent L remaining in the protruding part of the bypass part 11 reaches the rib 74a on the rear side through the rib 74a on the front side and adheres to the hand of the healthcare worker.

[0086] In addition, the space on the front side of the space in which the external thread 73 of the long part of the piston 71 is formed as the front end of the long part of the piston 71a having a cylindrical outer circular surface and the space on the rear side of the space in which the external thread 73 is formed as the rear end of the long part of the piston 71b having a cylindrical outer circular surface.

[0087] The front end of the long piston part 71a and the rear end of the long piston part 71b are made to have an outer diameter that is the same as or slightly smaller than the inner diameter of the internally threaded part 64 of the cylindrical part 63 of the handle 64. In this way, the front end of the long piston part 71a and the rear end of the long piston part 71b can be inserted into the internally threaded part 64 in in the direction of the axis of symmetry O.

[0088] In addition, a pair of guide plates 75 are formed at a mutual distance of 180° in the circular direction of the long piston part 71 on the outer peripheral surface of the rear end of the long piston part 71b. These guide plates 75 have a rectangular shape and protrude outward radially from the long part of the piston 71 in a section vertical to the axis of symmetry O and extend parallel to the axis of symmetry 0 along a predetermined length.

[0089] Next, a method of using the dual-chamber prefilled syringe 100 having the configuration described above will be described with reference to DRAWINGS 6A through 7B.

[0090] First, as shown in FIG. 6A, the connecting part 76 at the front end of the piston 70 is screwed into the internally threaded hole of the end plug 50 and thus the piston 70 is connected to the end plug 50. At this stage, the front end of the long part of the piston 71a of the long part of the piston 71 is inserted into the internally threaded part 64 of the handle 60.

[0091] Then, the pressure part 77 of the piston is pushed from the rear side when the healthcare worker rests his fingers on the flange part 62 of the handle 60. The pressure force is transmitted to the middle plug 40 via the end plug 50 and the solvent L. Namely, the piston 70 moves forward due to the pressure force described above and the middle plug 40 also moves forward in the rear part of the cylinder 13 of the cylinder 10.

[0092] As shown in FIG. 6B, at the time when the middle plug part 40 (in this embodiment, the half of the middle plug 40 from the front side in the direction of the axis of symmetry O) enters the bypass part 11, the front end of the externally threaded part 73 of the piston 70 is brought into contact with the rear end of the internally threaded part 64 of the handle 60. The externally threaded part 73 can be brought into contact with the internal threaded part 64 when the front end of the intermediate plug 40 reaches the rear end of the bypass portion 11 or when the externally threaded portion 73 can reach the internally threaded portion just before the front end of the middle plug 40 reaches the rear end of the bypass portion 11. In this way, by bringing the externally threaded portion 73 and the internally threaded portion 64 into contact, the externally threaded portion 73 and the internally threaded portion 64 become stop elements for further displacement forward of the piston 70. The piston 70 then cannot go forward even when the piston 70 is pressed.

[0093] In addition, by bringing the externally threaded portion 73 and the internally threaded portion 64 into contact in this manner, the externally threaded portion 73 and the internally threaded portion 64 can be screwed together. Thus, when the piston 70 rotates toward the front side in the screw rotation direction, the externally threaded portion 73 and the internally threaded portion 64 are the screw and the piston 70 moves forward in accordance with the pitch of the thread. The end plug 50 is also moved forward by moving the piston 70 as shown in FIG. 6C, when the entire length of the middle plug 40 in the direction of the axis of symmetry O enters the bypass part 11, the front chamber F and the back chamber B mutually traffic over the outwardly protruding space of the cylinder 10 in the bypass part 11.

[0094] Accordingly, the solvent L from the rear chamber F is allowed to flow to the preparation S in the front chamber F. In addition, when the piston 70 is further rotated in the direction of rotation by the screw and gradually moves forward, most of the pressure force acting on the solvent L due to the forward movement of the piston 70 is converted into pressure that allows the solvent L to flow into the front chamber F. Therefore, the middle plug 40 remains in the bypass part 11 with a small forward movement.

[0095] Thereafter, at the moment when the front end of the end plug 50 is brought into contact with the rear end of the middle plug 40 by moving the piston 70 forward, the entire solvent from the rear chamber B is introduced into the preparation in the front chamber F and thus the rear chamber B is eliminated. Furthermore, when the piston 70 is further rotated in the direction of rotation by the screw and gradually moves forward, the middle plug 40 which is brought into contact with the end plug 50 is also simultaneously moved. forward over end plug 50.

[0096] Then, as shown in FIG. 7A, at the moment when the part of the middle plug 40 (in this embodiment, the half of the middle plug 40 from the front side in the direction of the axis of symmetry O) enters the front part of the cylinder 12 of the cylinder 10, namely at the moment when the part of the middle plug 40 comes out of the bypass part 11, the guide plates of the piston 70 are brought into contact with the slightly inclined surface 66a of the first protrusions 66 of the handle 60 so that they can pass over from the back in the direction of rotation by screwing. At that time, the anterior chamber F is hermetically sealed again and the healthcare professional then shakes the two-chamber pre-filled syringe 100 and the injection preparation M is completed.

[0097] Here, the state in which the guide plate 75 is brought into contact with the first protrusion 66 so as to be able to cross it means the state of contact at the level when, although there is resistance to the rotation of the piston 70 due to the fact that the guide plate is brought into contact with the slightly inclined surface 66a, the guide plate 75 can pass over the first protrusion 66 to the front side in the direction of rotation by strongly rotating the piston 70. Such the contact state can be achieved by casting the piston 70 and handle from some elastic material such as synthetic resin.

[0098] In the above-described state of contact when the guide plate 7 crosses the first protrusion 66 by strongly rotating the piston 70 as shown in FIG. 8, the guide plate is then brought into contact with the vertical surface 67a of the second protrusion 67 from the rear side in the direction of rotation by screwing. Therefore, the movement of the guide plate 75 towards the front side in the direction of rotation by screwing is disabled. Namely, the piston 70 can no longer turn forward in the direction of rotation by screwing. Even when the piston 70 rotates in the opposite direction of rotation by the screw, the guide plate is brought into contact with the steep inclined surface 66a of the first projection 66 and thus the rotation is prevented.

[0099] Further, after the guide plate 75 passes over the first protrusion 66 as described above, the externally threaded portion 73 has passed through the space in which the internally threaded portion 64 is located. Namely, there is a release from screwing between the externally threaded portion 73 and the internally threaded portion 64. In addition, when the guide plate 75 is placed between the first and second protrusions 66, the position of the guide plate 75 in the circular direction coincides with the guide groove 65 of the handle 60. Namely, the guide plate 75 and the guide groove 65 can be wedged together.

[0100] Thus, the piston 70 can again be pressed to go straight.

[0101] Then, when the piston 70 is pressed, the guide plate 75 of the piston 70 is wedged into the guide groove 65 of the handle 60 and the piston 70 moves forward guided by the guide groove 65. The pressure force generated by pushing the piston 70 is then transmitted to the front plug 30 via the end plug 50, the middle plug 40 and the injection M and the front plug 30 moves forward into cylinder 10.

[0102] When the front cap 30 enters the bypass chamber 25, thanks to the forward movement of the front cap 30 described above, the front chamber F in which the injection M is located communicates with the introduction opening 23a of the luer tip 23 via the bypass groove 26. Thus, the bubbles remaining in the cylinder 10 are thrown out and the injection M can be introduced into the injection needle 27 and the injection M can be inject the patient.

[0103] After that, when injecting the injection M, the piston 70 is pushed further and thus the injection M from the front chamber F is introduced into the injection needle 27 via the bypass groove 26 and the introduction opening 23a. Finally, when the piston 70 is fully depressed, as shown in FIG. 7B, the entire injection M is injected into the patient through the injection needle 27 and the front end of the middle plug 40 and the rear end of the front plug 30 are brought into contact with each other thereby eliminating the anterior chamber F. As described above, the injection of M to the patient is completed.

[0104] According to the two-chamber pre-filled syringe 100 of this embodiment having the configuration described above, when the piston 70 rotates in accordance with the rotation of the external thread part 73 and the internal thread part 64, the piston 70 gradually moves forward in accordance with the step of the external thread part 73 and the internal thread part 64. Therefore, it is possible to avoid excessive worry of the piston 70 moving forward. and it is possible to allow the middle plug 40 to remain in the bypass part 11. Thus, it is possible to ensure communication between the front chamber F and the back chamber B and thus it is possible to properly (or completely) mix the solvent L and the preparation S.

[0105] Here, when aripiprazole is used as preparation S, it is difficult to dissolve in solvent L. However, in the two-chamber prefilled syringe 100 of this embodiment, preparation S can be properly (or completely) dissolved in solvent L. Therefore, even when aripiprazole is used as preparation S that is difficult to dissolve in solvent L, aripiprazole can be easily suspended in solvent L.

[0106] In addition, when the middle plug 40 is moved forward over the end plug 50 and solution L by pushing the piston 70, the externally threaded portion 73 comes into contact with the internally threaded portion 64 when the intermediate plug portion 40 enters the bypass portion 11. Therefore, even if the piston 70 is pressed further, the piston 70 does not move forward and the intermediate plug 40 does not move either. forward. Therefore, it is possible to avoid that the middle plug 40 moves forward too far towards the front side of the bypass chamber 11 due to the excessive force exerted on the piston 70.

[0107] In addition, the two-chamber pre-filled syringe 100 of this embodiment has a configuration in which, as described above, when one part of the middle cap 40 enters the bypass part 11 by moving forward by pushing the piston 70, the front end of the externally threaded part 73 comes to and is screwed into the front end of the internally threaded part 64. It is also possible to provide a configuration in which the front end of the externally threaded part the thread 73 reaches the internally threaded portion 64 just before the front end of the middle plug 40 enters the bypass portion 11.

[0108] Thus, after the piston 70 can rotate in accordance with the screwing of the externally threaded part 73 and the internally threaded part 64 only when the middle plug 40 reaches the bypass part 11 and when the solvent L is introduced into the preparation S, the piston 70 can be pressed only until the middle plug part 40 reaches the bypass part 11. In this way, it is possible to simplify the handling of the two-chamber pre-filled syringe 100.

[0109] In addition, in the two-chamber pre-filled syringe 100 according to this embodiment, when the piston 70 rotates and moves forward in accordance with the screwing of the externally threaded portion 73 and the internally threaded portion 64, the externally threaded portion 73 of the piston 70 passes through the internally threaded portion 64 of the handle 60, thereby releasing the screwing between the externally threaded portion. 73 and the internally threaded part 64. Then the guide plate 75 of the piston 70 is brought into contact with the second projection 67 of the handle 60 and the piston can no longer rotate. Therefore, the healthcare professional can easily recognize that there has been release from twisting between the externally threaded part 73 and the internally threaded part 64.

[0110] Further, after the warping has been released in this way, the piston 70 can be pressed. At that moment, the piston 70 is stopped in a position in which the guide plate 75 of the piston 70 and the guide groove 65 made on the internally threaded part 64 can engage each other, so that when the piston 70 is pressed, the piston 70 can be guided in the direction in which the guide groove 65 extends. Therefore, the piston 70 can go straight and the same action can be performed as in the case of ordinary syringes.

[0111] In addition, in this embodiment of the invention, in the case when the piston 70 rotates in accordance with the screwing between the externally threaded part 73 and the internally threaded part 64, the guide plate 75 of the piston 70 is brought into contact with the first projection 66 to pass over it when the middle plug 40, moving linearly with the cylinder 10, exits the bypass part 11. Thus, the health worker can easily recognize that the anterior chamber F is resealed after the intermediate plug 40 has moved over the bypass portion 11. Then the healthcare professional shakes the two-chamber pre-filled syringe 100 so that the injection M in which the preparation S is completely dissolved in the solvent L can be reconstituted.

[0112] Further, in this embodiment of the invention, as described above, a configuration is given in which the guide plate 75 passes over the first protrusion 66 by turning the piston 70 in accordance with the screwing of the internally threaded part 64 and the externally threaded part 73, after which there is a release from twisting between the externally threaded part 73 and the internally threaded part 64.

[0113] Thus, after a part of the middle plug 40 passes over the bypass part 11 due to the rotation of the piston 70, the piston 70 can be pressed again. In addition, after the guide plate 75 passes the first protrusion 66, the guide plate 75 comes into contact with the second protrusion 67 and thus the rotation piston 70 stops. This position becomes the position where forward motion is switched from rotary to straight-line motion.

[0114] In this way, the piston 70 rotates only when the solvent L is introduced into the preparation S and then the operation is switched to pushing the piston 70. It is possible to simplify the handling of the two-chamber pre-filled syringe 100.

[0115] In addition, in this embodiment, when by turning the piston 70, the guide plate 75 is brought into contact with the second protrusion 67, the guide plate 75 of the piston 70 is wedged into the guide groove 65 of the handle 60. Therefore, after that, by pushing the piston 70, the piston 70 cannot go straight.

[0116] As described above, the two-chamber pre-filled syringe 100 of this embodiment is used to allow the piston 70 to go straight when used to thereby allow the middle plug 40 to enter the bypass part 11 thereby allowing the solvent to flow safely into the preparation S and sufficiently dissolve or suspend the preparation S. Here, when the piston 70 only goes straight, it is difficult to adjust the force pushing the piston 70 so that there is a possibility that the middle plug 40 may pass through bypass 11.

[0117] In this embodiment of the invention, based on the contact of the externally threaded portion 73 and the internally threaded portion 64, the health care worker can detect the position where the middle plug 40 enters the bypass portion 11. In addition, the forward movement of the piston 70 is then performed by turning in accordance with the rotation of the externally threaded portion 73 and the internally threaded portion 64, and thus the speed can be easily adjusted and the advancing speed do not exceed the predetermined speed. Therefore, it is possible to avoid that the middle plug 40 passes through the bypass part 11. In particular, the two-chamber prefilled syringe 100 of this embodiment is suitable for use when it is a preparation S that is special and takes a long time to dissolve.

[0118] In addition, it is considered that if there is no guide plate 75 and other protrusions 67 when the externally threaded portion 73 passes through the internally threaded portion 64 and the engagement between the ends of the externally threaded portion 73 and the internally threaded portion 64, the health worker cannot recognize that there has been release from twisting of the externally threaded portion 73 and the internally threaded portion 64 and in that position piston 70 rotates again and again. In addition, when the healthcare worker notices the loosening of the thread and presses the piston 70 hastily, the injection M is instantly pressed after the piston 70 is free to go straight and thus the front plug descends into the bypass chamber 25 and the hermetic sealing of the front part is stopped. of the cylinder 10. Therefore, when the syringe is shaken, there is a fear that the solvent L or the injection M may fly out of the injection needle 27.

[0119] In view of this, in this embodiment of the invention, the guide plate 75 is brought into contact with the second projection 67 to stop the rotation of the piston 70, thus enabling the healthcare worker to detect that the release of the above-mentioned screw has occurred. That is why the healthcare worker can recognize without thinking carefully that it is necessary to no longer press the piston 70, that it is necessary to dissolve and suspend preparation S well by shaking preparation S and solvent L, and that it is necessary to carefully handle the syringe in order to expel the bubbles from that place and inject the medicine to the patient.

[0120] A two-chamber pre-filled syringe (aripiprazole pre-filled syringe) 100 which is an embodiment of the present invention is described in detail. The invention for which the patent application is made is not limited by it, and some changes in the construction and the like can be made on the examples of the patent implementation without deviating from the scope of the invention for which the patent application is made.

[0121] For example, the pitch of the externally threaded portion 73 and the internally threaded portion 64 can be constructed appropriately to adjust the forward movement speed of the piston 70 or freely adjust the dissolution or suspension speed of the preparation S solvent L.

[0122] Furthermore, in the case where the two-chamber pre-filled syringe 100 is packaged in a state where the plunger 70 is bonded with the end cap 50, even when the plunger 70 is carelessly pressed during transportation or the like, further forward movement of the plunger 70 is prevented after the externally threaded portion 73 comes into contact with the internally threaded portion 64. Therefore, it is always possible to safely keep the solvent apart. L and preparation S and avoid danger.

[0123] Preferably, the respective ends of the internally threaded portion 64 and the externally threaded portion 73 are circumferentially tapered. Therefore, the internal thread part 64 and the external thread part 73 will be able to be easily screwed together and thus this operation can be easily performed.

[0124] It is possible to use the handle 60 shown in FIGURES 9A and 9B, for example as the handle 60 of a modified embodiment. In this handle 60 of the second embodiment, a flanged part 62 is provided on the rear side of the cylindrical part 63 of a different design in which the cylindrical part 63 protrudes backwards from the flanged part 62. In other words, in the modified version, the cylindrical part is buried in the mounting part 61.

[0125] Because the cylindrical part 63 having the internally threaded part 64, the first protrusions 66, the second protrusions 67, and the guide groove 65 does not protrude from the flange part 62, it can be avoided that the handling of the two-chamber pre-filled syringe is problematic due to the health worker's fingers touching the cylindrical part 63.

[0126] According to embodiments of the two-chamber pre-filled syringe of the present invention, it is possible to properly mix the solvent and the preparation. In addition, judging by the aripiprazole filled in the syringe, it is possible to reduce the residue and incomplete dissolution during resuspension.

[0127] Examples

[0128] Examples will be described below.

[0129] The loose powder of aripiprazole hydrate was suspended in a dispersant to obtain a concentration of 30 wt. % as aripiprazole anhydride. The concentrations of other additives in the obtained suspension were as follows: the concentration of sodium carboxymethyl cellulose was about 1.248 wt.%, the concentration of mannitol was about 6.24 wt.%, and the concentration of sodium dihydrogen phosphate monohydrate was 0.111 wt.%. In addition, the pH of the suspension was adjusted to 7 by adding an aqueous solution of sodium hydroxide. The suspension was wet-pulverized at 550 bar in a high-shear rotary homogenizer (CLEARMIX, M Technique Co., Ltd.) and repeatedly wet-pulverized at 550 bar in a high-pressure homogenizer (Niro Inc.). The primary mean particle size of the resulting suspension was 2 to 3 pm.

[0130] 1.5 mL of the suspension (about 450 mg, as aripiprazole anhydride) was added to a freeze-drying vessel made of polyethylene and transferred to a lyophilizer. The suspension was freeze-dried according to the following cycle (a) and (b) to obtain a cake: (a) Heat treatment: the container filled with the suspension was frozen for about 4 hours and left

[0131] to stand at a temperature maintained at about -40°C, and

[0132] (b) Primary drying: primary drying continued for about 40 hours at a pressure raised in the chamber to about 13 Pa and at a temperature raised to about -5°C.

[0133] After lyophilization, the bottom of the vessel was pressed and a solid lyophilized cake was taken.

[0134] As preparation S, the lyophilized cake was placed in the front chamber (the space between the front cap 30 and the middle cap 40) of the two-chamber pre-filled syringe 100 of the embodiment of the invention. The back chamber (the space between the middle plug 40 and the end plug 50) was filled with 2.0 mL of purified water as solvent L.

[0135] 1. Measurement of dead space residual volume in a two-chamber prefilled syringe

[0136] The end plug 50 was pushed until the purified water from the rear chamber flowed into the front chamber via bypass 11. After the purified water flowed into the front chamber, the lyophilized cake was resuspended by sufficient shaking. After resuspending, no lumps of powder or similar residue caused by incomplete dissolution were shown in the suspension. By further depressing the end cap, the suspension was discharged through the inlet opening 23a of the luer tip 23 which was the discharge point at the front end of the two-chamber pre-filled syringe 100. After discharge, the two-chamber pre-filled syringe 100 was disassembled and the amount of drug remaining in the two-chamber pre-filled syringe 100 was determined. Procheck was about 19 mg. After the suspension has been well shaken and uniformly resuspended, this amount of drug is the amount remaining in the dead space in the syringe.

[0137] 2. Resuspension using a regular plunger

[0138] A plain plunger (not having the externally threaded portion 73 on it) which is pushed to move only unidirectionally in the direction of discharge was attached to the end plug 50 to make a comparative example of the two-chamber pre-filled syringe and the end plug 50 was pushed to allow the purified water to rapidly flow into the front chamber in the same manner as described above. Then the syringe was left for 5 seconds without complete shaking and the suspension was discharged through the inlet port 23a of the luer tip 23. After emptying, the two-chamber pre-filled syringe was unfolded and the amount of drug remaining in the two-chamber pre-filled syringe was determined. Prosecco was about 195 mg. It was found that about 176 mg, which is the difference from the residual amount described above, remains in the syringe as a residue due to incomplete dissolution.

[0139] 3. Resuspension using a threaded plunger

[0140] The threaded piston 70 of this embodiment of the invention is attached to the end plug 50 to allow purified water to flow rapidly into the chamber by turning the thread as described above in the embodiment of the invention. Then the syringe was left for 5 seconds without complete shaking and the suspension was discharged through the inlet port 23a of the luer tip 23. After emptying, the double-filled syringe was disassembled and the amount of drug remaining in the double-chambered pre-filled syringe was determined. Prosecco was about 62 mg. It was found that about 43 mg, which is the difference from the residual amount described above, remains in the syringe as a residue due to incomplete dissolution.

[0141] The result of the aforementioned test is shown in Table 1. From the results, it was determined that resuspension can be effectively performed by performing the resuspension procedure with the threaded piston 70 of this embodiment. In principle, with regard to the two-chamber pre-filled syringe, there is a concern that in actual clinical practice, when resuspension needs to be done by shaking as in the case of the preparation used in this trial, the injection may be performed without the shaking procedure. Forgetting the shaking, a significant reduction in dose was shown when a plain plunger was used. However, when using the piston 70 of this embodiment of the invention, this significant dose reduction becomes smaller even when shaking is forgotten. In addition, since the plunger 70 is activated differently before and after the resuspendation procedure, as opposed to a normal plunger that only pushes, it is possible to encourage the health care professional to recognize the phase of resuspendation and thus it is possible to reduce the risk of dose reduction due to forgetting to shake.

[0142] List of reference marks

[0143] 10 cylinder, 11 bypass part, 12 front part of cylinder, 13 rear part of cylinder, 14 annular overhang at the front end, 15 annular overhang at the rear end, 20 luer-lock extension, 21 base, 22 cylinder part, 23 luer tip, 24 insertion hole, 25 bypass chamber, 25a front surface, 26 bypass groove, 26a rectilinear groove, 26b circular groove, 27 pin, 30 front plug, 40 middle plug, 50 end plug, 60 handle, 61 mounting part, 62 flange part, 63 cylinder part, 64 internal thread part, 65 guide groove, 66 first protrusion, 66a slightly sloping surface, 66b steeply sloping surface, 67 second projection, 67a certical surface, 70 piston, 71 long piston part, 71a front part of long piston part, 41b rear part of long piston part, 73 externally threaded part, 74 cutout, 74a rib, 75 guide plate, 76 connecting part, 77 pressure part, 100 two-chamber forward Flexible syringe, O axis of symmetry, S preparation, L solvent, M injection, F anterior chamber, B posterior chamber.

Claims (5)

1. A two-chamber pre-filled syringe (100) consisting of: a cylinder (10) having a cylindrical shape with the axis of symmetry (O) as the center and having a bypass part (11) formed due to the protrusion of a part of the inner circular surface to the outside; a luer-lock extension (20) located at the front end of the cylinder; a handle (60) located at the rear end of the cylinder; front plug (30) which is fitted at the front end of the bypass part of the cylinder; the middle plug (40) which is arranged at the rear end of the bypass part of the cylinder to hermetically close the preparation (S) together with the front plug; a rear plug (50) which is fitted to the rear of the middle plug in the cylinder to hermetically seal the solvent together with the middle plug; piston (70) which is connected with the rear plug from the rear side by inserting the handle; an internally threaded portion (64) configured to rotate about an axis of symmetry on the inner peripheral surface of the handle; and an externally threaded portion (73) made to be threaded internally on the outer circular surface of the piston, characterized by including a guide groove (65) formed on the internally threaded portion and extending parallel to the axis of symmetry; guide plate (75) which is formed on the rear side of the externally threaded part on the outer peripheral surface of the piston and which is guided in accordance with the guide groove; and the first protrusion (66) formed at the rear end of the handle and with which the guide plate is placed so that it comes into contact with it and passes over it when at least one part of the middle plug, which by turning the piston according to the turning of the part with internal thread and part with external thread, moves forward along the bypass part. 2. A two-chamber prefilled syringe according to claim 1, wherein the front end of the externally threaded portion is arranged to reach the rear end of the internally threaded portion and can be screwed in when the intermediate plug, which is moved forward by pushing the piston, enters the bypass portion. 3. A two-chamber pre-filled syringe according to Claim 1 or Claim 2 wherein the screw between the externally threaded portion and the internally threaded portion is arranged such that release occurs after the guide plate passes the first protrusion by rotating the plunger in accordance with the internally threaded portion and the externally threaded portion. 4. A two-chamber pre-filled syringe according to claim 3 comprising: a second projection (67) formed at the rear end of the handle and adapted to be brought into contact at a point where the guide plate passing over the first projection can be placed in the guide groove. 5. A two-chamber pre-filled syringe according to one of Claims 1 to 4, wherein the preparation includes aripiprazole.